Sodium hydride → HCID 71008016, compound

HRID 2408710Notes

Reaction equation

HRID 2408710 reaction equation
[CH3:1][C:2]1[C:10]2[NH:9][C:8]3[CH2:11][CH2:12][N:13]4[CH:17]([C:7]=3[C:6]=2[CH:5]=[C:4]([CH3:18])[CH:3]=1)[CH2:16][CH2:15][CH2:14]4.[H-].[Na+].[O:21]1[CH2:23][CH:22]1[C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1>CN(C=O)C>[CH3:1][C:2]1[C:10]2[N:9]([CH2:23][CH:22]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[OH:21])[C:8]3[CH2:11][CH2:12][N:13]4[CH:17]([C:7]=3[C:6]=2[CH:5]=[C:4]([CH3:18])[CH:3]=1)[CH2:16][CH2:15][CH2:14]4

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 71268678HCID 71268678, compound

Product 1

HCID 71008016HCID 71008016, compoundYield 18.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8,10-Dimethyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (700 mg, 2.92 mmol) in DMF (20 mL) was stirred at 0° C. for 5 min. NaH (580 mg, 14.60 mmol) was added slowly at 0° C. After 10 min. stirring, 4-(oxiran-2-yl)pyridine (710 mg, 5.87 mmol) was added and the reaction mixture was stirred at RT for 15 h. The reaction mixture was poured in ice-cold water (150 mL) and extracted with EtOAc (3×200 mL). The combined organic layer was washed with water (6×300 mL), dried over anhydrous sodium sulfate and concentrated to obtain semi-solid residue that was washed with hexane (3×20 mL). The residue was suspended in ether (30 mL) stirred for 1 h. The suspension was filtered to give 200 mg of 2-(8,10-dimethyl-2,3,5,6-tetrahydro-1H-indolizino[7,8-b]indol-7(11cH)-yl)-1-(pyridin-4-yl)ethanol. 1H NMR (CD3OD, HCl salt) δ (ppm): 8.79 (d, 2H), 8.03 (d, 2H), 7.13 (s, 1H), 6.82 (s, 1H), 5.22 (dd, 1H), 5.01 (t, 1H), 4.67 (dd, 1H), 4.48 (dd, 1H), 4.79 (m, 1H), 3.64 (t, 2H), 3.4 (m, 3H), 2.9 (m, 1H), 2.73 (s, 3H), 2.37 (s, 3H), 2.22 (m, 3H). Separation by chiral HPLC provided diastereomers II-125a-b.

Workup

  1. stirringthe reaction mixture was stirred at RT for 15 h
  2. extractionextracted with EtOAc (3×200 mL)
  3. washThe combined organic layer was washed with water (6×300 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto obtain semi-solid residue that
  7. washwas washed with hexane (3×20 mL)
  8. stirringstirred for 1 h
  9. filtrationThe suspension was filtered

Sources & evidence

ORD record
ord-1eaff884bd444a61912855a00b155fed
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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